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Chapter 18 : Poxviruses
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Vaccinia virus (VACV) and cowpox virus (CPXV) are distinct orthopoxviruses that cause human infections, and one is not a synonym for the other. Poxvirus virions appear to be oval or brick-shaped structures of about 200 to 400 nm in length with axial ratios of 1.2 to 1.7. The structure of VACV is characteristic of that of all the poxviruses that infect humans except those belonging to the genus Parapoxvirus. In studies of human monkeypox carried out in Zaire between 1981 and 1986, twenty-seven of 136 (20%) persons gave no history of illness, residual skin lesions, or other changes suggestive of monkeypox, and therefore were classified as having subclinical infections. Human infections with bovine pustular stomatitis virus (BPSV) are less common than with the other two parapoxviruses that infect humans, probably because contact between animal handlers and lesions of BPSV are less common than those of shearers with orf and milkers with milker's nodules. The major diagnostic criteria for poxvirus infections are the size and morphology of the poxvirus virion in negatively stained preparations viewed with an electron microscope. Historically, antigen detection protocols rarely could differentiate poxviruses at the species level. Most importantly, Cidofovir (CDV) and hexadecyloxypropyl (HDP)-CDV have broad-spectrum activity against viruses that encode DNA polymerases, including all poxviruses known to infect humans, adenoviruses, and many herpesviruses. The effectiveness of the egress inhibitor ST-246 against poxviruses of other genera will depend on the importance of the cell-to-cell spread of virus in the disease process.
Structure of virions of poxviruses that cause human infections. Shown are negatively stained preparations of orthopoxvirus virions (cowpox, monkeypox, vaccinia, and variola viruses) (A), parapoxvirus virions (ORFV, BPSV, PCPV, and sealpox viruses) (B), and yatapoxvirus virions (TANV and YMTV) (C). The virions of orthopoxviruses and yatapoxviruses have similar morphologies, but those of yatapoxviruses always have two membranes. Virions of the parapoxviruses are smaller and have a distinctive regular surface structure. (D) Diagram of the structure of the virion of VACV. The viral DNA and several proteins within the core are organized as a nucleosome. The core has a 9-nm-thick shell with a regular subunit structure. Within the virion, the core assumes the shape of a dumbbell because of the large lateral bodies, which are, in turn, enclosed within a protein shell about 12 nm thick—the first membrane, the surface of which appears to consist of irregularly arranged surface tubules, which, in turn, consist of small globular subunits. Mature virus released by exocytosis (extracellular enveloped virus) is enclosed within a second membrane (envelope) acquired from the Golgi. This membrane contains host cell lipids and several unique virus-specific polypeptides not found in the intracellular mature virus outer membrane. Most virions remain cell associated and are released by cellular disruption, without the second membrane. (E) Diagram of the structure of the virion of ORFV. The first membrane consists of a single long tubule that appears to be wound around the particle. In negatively stained preparations (B) both sides are visible, giving a characteristic criss-cross appearance. The second membrane is usually closely applied to the surface of the first membrane. Bar = 100 nm. (Reprinted from reference 39a with permission.)
Diagram illustrating the replication cycle of vaccinia virus, the prototype orthopoxvirus. (Reprinted from reference 98 with permission.)
Diagram illustrating the epidemiology of cowpox and buffalopox. Solid lines represent known paths of transmission; broken lines represent presumed or possible paths of transmission. (A) Identified wild-rodent reservoir hosts of cowpox include bank voles, wood mice, and shorttailed voles in Great Britain and probably elsewhere in Europe, lemmings in Norway, and susliks and gerbils in Turkmenistan. The traditional liaison hosts from which humans were infected were cows, but currently the most common liaison hosts are domestic cats. White rats, the source of disastrous outbreaks in animals in the Moscow Zoo in 1973 and 1974 ( 88 ), probably acquired infection from wild-rodent-contaminated straw or other bedding material. (B) In India, Egypt, and Indonesia, in the days of smallpox vaccination, buffaloes were sometimes infected with vaccinia virus from recently vaccinated humans, causing what was called buffalopox. Buffalopox seems to have disappeared in Indonesia and Egypt but is still a problem in several states of India. Since the cessation of vaccination, infected buffaloes constitute a source of infection of humans. It is possible that the virus can be maintained by serial transmission in buffaloes, but on the analogy of cowpox in Europe, it is possible that there is an unknown rodent reservoir. (Reprinted from reference 140 with permission.)
Diagrammatic representation of the mode of spread of ectromelia virus through the body in mousepox. (Reprinted from reference 38 with permission.)
Section of a skin lesion of molluscum contagiosum. (Courtesy of D. Lowy.)
Clinical features of smallpox and monkeypox. (Left) The rash of smallpox in a boy in Zaire. (Middle and right) Front and rear views of a 7-year-old girl from Zaire with monkeypox, on the eighth day after the appearance of the rash. Note the enlargement of the cervical and inguinal lymph nodes, a feature not seen in smallpox. (Middle and right panels reprinted from reference 11 with permission.)
Localized zoonotic infections with poxviruses. (A and B) Lesions on hands acquired by milking infected cows: cowpox, caused by an orthopoxvirus (A), and milker’s nodes, caused by a parapoxvirus, PCPV (B). (C) Parapoxvirus lesion of ORFV, acquired by handling sheep or goats suffering from contagious pustular dermatitis. (D) Lesion of tanapox on an arm of a child in the DRC. The virus was transmitted mechanically by mosquitoes from an animal reservoir host. (Panels A and B courtesy of D. Baxby; panel C courtesy of J. Nagington; panel D courtesy of Z. Jezek.)
Primary response to vaccination; typical vesiculo-pustular response, maximal at 8 to 11 days. (Left) Response at 7 days; (right) response at 11 days. (Courtesy of J. R. L. Forsyth.)
Molluscum contagiosum lesions. (Courtesy of E. C. Siegfried.)
Severe complications of vaccination. (A) Eczema vaccinatum in an unvaccinated sibling of a vaccinated individual. (B) Progressive vaccinia (vaccinia gangrenosum), which was fatal in a child with a congenital defect in cell-mediated immunity. (C) Generalized vaccinia, 10 days after primary vaccination; benign course, no scarring. (D) Ocular vaccinia after autoinoculation. (Reprinted from reference 41 with permission.)
Poxviruses that can cause disease in humans
Complications of smallpox vaccination in the United States in 1968